We request a third generation cyclotron to meet current research demands and expand application of accelerator-produced radionuclides. The instrument will increase our ability to produce radiotracers for the broader scientific community. Many researchers throughout the University of Pennsylvania, who receive considerable support from the NIH, have recognized the opportunities molecular imaging presents as a non-invasive analytical tool for measuring biochemical and physiological phenomena in vivo. Demand has significantly increased and continues to grow; our cyclotron, procured with NIH support in 1985, has reached capacity. The molecular imaging program at Penn has grown substantially; numerous radiotracers are being synthesized for pre-clinical and clinical research. We have an active Imaging Probe Synthesis Core for human and animal research, which relies heavily on timely and sufficient production of adequate quantities of radionuclides. We also have successfully translated a number of promising radiotracers through pre-clinical models into clinical research studies. However, our current ability to produce amounts of radiotracers in adequate amounts has been rate-limiting to translational research. Progress necessitates a modern facility that will enable production of novel positron emitters in quantities not feasible with the current cyclotron. The proposed instrument will ensure sufficient radionuclide and radiotracer production to support the growth in our molecular imaging program and thus substantially enhance ongoing research; increase the ability to pursue proof-of-principle research; effect a substantial impact in molecular imaging within a multitude of disciplines, and allow the existing cyclotron to be exploited for novel isotope development. [unreadable] PUBLIC HEALTH RELEVANCE: Our translational research program in molecular imaging has provided key insights into biologic processes in both animal studies and in clinical research. For continued growth, we need a new cyclotron, which will allow us to increase production, resulting in new radiotracers that increase scientific understanding and ultimately provide clinicians with unique diagnostic tools. [unreadable] [unreadable] [unreadable]